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Published on: May 31, 2018

Ubiquitin-specific protease 2-69 in macrophages potentially modulates metainflammation

Hiroshi Kitamura1, Shunsuke Kimura, Yoshinori Shimamoto

  • 11Department of Comparative and Experimental Medicine, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. ktmr@med.nagoya-cu.ac.jp.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|September 6, 2013
PubMed

Insights

Ubiquitin specific protease (USP) 2-69, a novel molecule, was identified to suppress meta-inflammatory molecules. USP2-69 plays a role in modulating pathways implicated in metabolic disorders and chronic inflammation.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Metabolic Disease Research

Background:

  • Macrophages are key players in chronic inflammation and metabolic diseases.
  • Ubiquitin specific protease (USP) 2 is implicated in cellular processes.
  • Understanding USP2's role can offer insights into metabolic disorder treatments.

Purpose of the Study:

  • To identify novel molecules modulating metabolic disorder pathways.
  • To investigate the role of ubiquitin specific protease (USP) 2-69 in inflammation and metabolic diseases.
  • To elucidate the anti-inflammatory properties of USP2.

Main Methods:

  • Short hairpin RNA-mediated knockdown (KD) of USP2 gene in human myeloid cell lines.
  • Overexpression of USP2-69 in human myeloid cell lines.
  • Analysis of gene expression (aP2/FABP4, PAI-1/SERPINE1, IL6, SAA3) in cell lines and adipose tissue.
  • Assessment of macrophage count in mesenteric adipose tissue of USP2-69 transgenic mice.
  • Chromatin analysis (accessibility, histone methylation, and acetylation) at the aP2 locus.

Main Results:

  • USP2 gene knockdown increased aP2/FABP4 and PAI-1/SERPINE1 expression, while USP2-69 overexpression alleviated this.
  • USP2 knockdown-derived supernatants induced IL6 and SAA3 in adipocytes, indicating anti-inflammatory effects of USP2.
  • USP2-69 transgenic mice showed reduced macrophage counts and decreased aP2/PAI-1 transcription in adipose tissue under high-fat diet.
  • USP2 knockdown led to increased chromatin accessibility, H3K4 methylation, and H4 acetylation at the aP2 locus.

Conclusions:

  • USP2-69 functions as a suppressor of meta-inflammatory molecules.
  • USP2-69 plays a significant role in modulating pathways relevant to type-2 diabetes development.
  • USP2-69 exhibits anti-inflammatory properties and influences macrophage behavior in adipose tissue.
Keywords:
aP2diabetesepigenetic control

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